{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T03:22:12Z","timestamp":1790392932634,"version":"4.1.0"},"reference-count":33,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2000,1,1]],"date-time":"2000-01-01T00:00:00Z","timestamp":946684800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2000,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>We show that LPS-stimulated circulating CD14-positive monocytes from patients with common variable immunodeficiency (CVID) express a higher proportion of intracellular IL-12-positive cells than monocytes from patients with X-linked agammaglobulinemia or normal subjects. We used four-color flow cytometry and measured IL-12 with an Ab to the p40 subunit following stimulation with LPS. The raised IL-12 is associated with an increased frequency of IFN-\u03b3-positive T cells, but not of IFN-\u03b3-positive CD56+ NK cells. These increases in frequency of cytokine-positive cells are due to a decrease in the absolute numbers of circulating monocytes and T cells that are negative for IL-12 and IFN-\u03b3, respectively. The increased frequency of IL-12-positive monocytes appears to be selective because TNF-\u03b1 was not increased, and is thus unlikely to reflect a general activation. Chronic infection is also unlikely to explain our data since cells from X-linked agammaglobulinemia patients with a similar Ig deficiency do not show these changes. Our data suggest a fundamental abnormality in the IL-12\/IFN-\u03b3 circuit in CVID, with up-regulation of IL-12 being the \u201cprimary\u201d factor. This imbalance is likely to skew the immune response away from Ab production and also explains the failure of CVID T cells to make Ag-specific memory cells and the chronic inflammatory and granulomatous complications that are a feature of CVID. This disease appears to be a rare example of a polarized Th1-type response and may in part be due to a genetic defect in the control of IL-12 production.<\/jats:p>","DOI":"10.4049\/jimmunol.164.1.488","type":"journal-article","created":{"date-parts":[[2014,4,21]],"date-time":"2014-04-21T18:07:57Z","timestamp":1398103677000},"page":"488-494","source":"Crossref","is-referenced-by-count":77,"title":["Up-Regulation of IL-12 in Monocytes: A Fundamental Defect in Common Variable Immunodeficiency"],"prefix":"10.1093","volume":"164","author":[{"given":"Rosario","family":"Cambronero","sequence":"first","affiliation":[{"name":"Department of Immunology, Medical Research Council Immunodeficiency Research Group, Royal Free & University College School of Medicine , London ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W A Carrock","family":"Sewell","sequence":"additional","affiliation":[{"name":"Department of Immunology, Medical Research Council Immunodeficiency Research Group, Royal Free & University College School of Medicine , London ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaret E","family":"North","sequence":"additional","affiliation":[{"name":"Department of Immunology, Medical Research Council Immunodeficiency Research Group, Royal Free & University College School of Medicine , London ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A David B","family":"Webster","sequence":"additional","affiliation":[{"name":"Department of Immunology, Medical Research Council Immunodeficiency Research Group, Royal Free & University College School of Medicine , London ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Farrant","sequence":"additional","affiliation":[{"name":"Department of Immunology, Medical Research Council Immunodeficiency Research Group, Royal Free & University College School of Medicine , London ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2000,1,1]]},"reference":[{"key":"2026020906021556300_R1"},{"key":"2026020906021556300_R2","first-page":"235","volume-title":"N. 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